Nitroarylhydroxymethylphosphonic acids as inhibitors of CD45.
A series of nitroarylhydroxymethylphosphonic acids was synthesized and evaluated as inhibitors of CD45. It was discovered that both the alpha hydroxy and nitro groups are essential for activity. Potency is enhanced by the addition of a large lipophilic group on the aryl ring adjacent to the phosphonic acid moiety. Kinetics studies have shown that these compounds are competitive inhibitors and thus bind at the active site of this enzyme.
Beers
S A
SA
R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
Malloy
E A
EA
Wu
W
W
Wachter
M P
MP
Gunnia
U
U
Cavender
D
D
Harris
C
C
Davis
J
J
Brosius
R
R
Pellegrino-Gensey
J L
JL
Siekierka
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009578:Nitrobenzenes / Q000138:chemical synthesis* / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D018411:Spodoptera
D009578:Nitrobenzenes; D063065:Organophosphonates; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens